We propose an investigation of morphogenetic mechanisms in the cellular slime mold, Dictyostelium discoideum. This primitive soil organism exists as a dispersion of amebae until its source of food (typically, bacteria) is exhausted. Starvation induces the cells to differentiate. They develop the capacity to come together and to form a succession of specific multicellular structures. Long range signalling between dispersed amebae utilizes extracellular cyclic AMP as a positive chemotactant. Tissue structures in the multicellular stages may also use secreted ligands to guide morphogenetic movement, but this is not known. Specific intercellular contacts guide early cell aggregation and could play a role in later tissue patterning. The major components in this study are three: 1. We intend to elucidate the mechanisms by which extracellular cyclic AMP elicits from suitably differentiated amebae a relay (amplification) response, the secretion of additional cyclic AMP. (It is this process which propagates the chemotactic signal over large distances.) The relay response will be characterized in whole cells, membranes and, if possible, at the macromolecular level. The role of adenylate cyclase and cell surface phosphodiesterase are of particular interest. 2. We seek to define rules describing morphogenesis. Controlled manipulations which evoke specific alterations in tissue pattern formation will be used to analyze formal mechanisms. Our conceptual framework extends the paradigm generated from studies of early aggregation; that is, sustained intercellular signalling via secreted small chemotactic molecules (morphogens). 3. Electron microscopic analysis will be used to define intercellular, surface contacts and histologic relationships between contiguous cells in various tissues and stages.